期刊
NEUROSCIENCE LETTERS
卷 392, 期 1-2, 页码 135-139出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2005.09.002
关键词
nicotinic receptors; mecamylamine; receptor protection assays
资金
- NIDA NIH HHS [DA10569] Funding Source: Medline
Studies involving receptor protection have been used to define the functional involvement of specific receptor subtypes in tissues expressing multiple receptor subtypes. Previous functional studies from our laboratory demonstrate the feasibility of this approach when applied to neuronal tissues expressing multiple nicotinic acetylcholine receptors (nAChRs). In the current studies, the ability of a variety of nAChR agonists and antagonists to protect native and recombinant alpha 3 beta 4 nAChRs from alkylation were investigated using nAChR binding techniques. Alkylation of native alpha 3 beta 4* nAChRs from membrane preparations of bovine adrenal chromaffin cells resulted in a complete loss of specific [H-3]epibatidine binding. This loss of binding to native nAChRs was preventable by pretreatment with the agonists, carbachol or nicotine. The partial agonist, cytisine, produced partial protection. Several nAChR antagonists were also tested for their ability to protect. Hexamethonium and decamethonium were without protective activity while mecamylamine and tubocurarine were partially effective. Addition protection studies were per-formed on recombinant alpha 3 beta 4 nAChRs. As with native alpha 3 beta 4* nAChRs, alkylation produced a complete loss of specific [H-3]epibatidine binding to recombinant alpha 3 beta 4 nAChRs which was preventable by pretreatment with nicotine. However, unlike native alpha 3 beta 4* nAChRs, cytisine and mecamylamine, provide no protection for alkylation. These results highlight the differences between native alpha 3 beta 4* nAChRs and recombinant alpha 3 beta 4 nAChRs and support the use of protection assays to characterize native nAChR subpopulations. (C) 2005 Elsevier Ireland Ltd. All rights reserved.
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